Study of the relationship between lesion severity and behavioral response to dopaminergic treatment in an animal model of Parkinson´s disease

CELIA LARRAMENDY; FLOOR SPANS; MARIANO SABORIDO; GABRIEL NEIMAN; IRENE TARAVINI; GUSTAVO MURER; OSCAR GERSHANIK

Huerta Grande-Córdoba

Congreso; I Reunión Conjunta de Neurociencias (IRCN); 2009

Taller Argentino de Neurociencias y Sociedad Argentina de Investigación en Neurociencias

<!-- /* Font Definitions */ @font-face {font-family:Calibri; panose-1:2 15 5 2 2 2 4 3 2 4; mso-font-charset:0; mso-generic-font-family:swiss; mso-font-pitch:variable; mso-font-signature:-1610611985 1073750139 0 0 159 0;} /* Style Definitions */ p.MsoNormal, li.MsoNormal, div.MsoNormal {mso-style-parent:""; margin-top:0cm; margin-right:0cm; margin-bottom:10.0pt; margin-left:0cm; line-height:115%; mso-pagination:widow-orphan; font-size:11.0pt; font-family:Calibri; mso-fareast-font-family:"Times New Roman"; mso-bidi-font-family:"Times New Roman"; mso-ansi-language:ES-AR; mso-fareast-language:EN-US;} span.Normaal {mso-style-name:Normaal; mso-ansi-font-size:11.0pt; font-family:Calibri; mso-ascii-font-family:Calibri; mso-hansi-font-family:Calibri; mso-bidi-font-family:"Times New Roman";} p.NoSpacing, li.NoSpacing, div.NoSpacing {mso-style-name:"No Spacing"; mso-style-parent:""; mso-style-link:"No Spacing Char"; margin:0cm; margin-bottom:.0001pt; mso-pagination:widow-orphan; font-size:11.0pt; font-family:Calibri; mso-fareast-font-family:Calibri; mso-bidi-font-family:"Times New Roman"; mso-ansi-language:NL; mso-fareast-language:EN-US;} span.NoSpacingChar {mso-style-name:"No Spacing Char"; mso-style-locked:yes; mso-style-link:"No Spacing"; mso-ansi-font-size:11.0pt; mso-bidi-font-size:11.0pt; font-family:Calibri; mso-ascii-font-family:Calibri; mso-fareast-font-family:Calibri; mso-hansi-font-family:Calibri; mso-ansi-language:NL; mso-fareast-language:EN-US; mso-bidi-language:AR-SA;} @page Section1 {size:612.0pt 792.0pt; margin:70.85pt 3.0cm 70.85pt 3.0cm; mso-header-margin:36.0pt; mso-footer-margin:36.0pt; mso-paper-source:0;} div.Section1 {page:Section1;} --> Parkinson’s disease is characterized by degeneration of dopaminergic neurons of the nigrostriatal pathway. The main symptoms are bradykinesia, rigidity, resting tremor and postural instability. We studied the relationship between the effects of levodopa and the D2 agonist pramipexole on behavioral deficits and lesion severity. Male Wistar rats received three unilateral 6-hydroxydopamine (6-OHDA) injections in the striatum. Rats were randomly assigned to a three week treatment either with water, levodopa or pramipexole. The cylinder test was performed to study the improvement of the akinesia of the affected contralateral forelimb under treatment. After being sacrificed, immunohistochemistry for tyrosine hydroxylase was performed on the substantia nigra, and the percentage of remaining cells compared to the control hemisphere was determined. Treatment with levodopa or pramipexole improved the akinesia of the contralateral forelimb in the cylinder test to normal levels in some animals. The three unilateral 6-OHDA injections in the striatum produced the degeneration of the nigrostriatal pathway resulting in remaining neuronal populations of 20-60% compared to the control hemisphere. We found that there was a significant correlation between the degree of TH positive cells loss and the use of the contralateral forelimb only in the pramipexole treated animals. D2-agonist mediated responses are known to be facilitated by concomitant D1 stimulation by either endogenous dopamine or a D1-agonist. Our findings support this hypothesis as the D2 receptor agonist pramipexole was unable to induce reversion responses in rats with low percentages of remaining cells, while with levodopa this was not the case.